title: Role of the cellular transcription factor YY1 in the latent-lytic switch of Kaposi's sarcoma-associated herpesvirus.
abstract: Lytic cycle reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) is initiated by expression of the ORF50 gene. Here we show that YY1 protein specifically binds to the ORF50 promoter (ORF50p) region in vitro and in vivo. After treatment with chemical inducers, including sodium butyrate (SB) and TPA, the levels of YY1 protein are inversely correlated with the lytic induction of KSHV in cells. Overexpression of YY1 completely blocks the ORF50p activation in transient reporter assays, while mutation at the YY1 site in the ORF50p or knockdown of YY1 protein confers an enhancement of the ORF50p activation induced by SB and TPA. YY1 overexpression in a stable cell clone HH-B2(Dox-YY1) also inhibits expression of the ORF50 and its downstream lytic genes. On the other hand, a chimeric YY1 construct that links to its coactivator E1A can disrupt viral latency. These results imply that YY1 is involved in the regulation of KSHV reactivation.
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Taoyuan, Taiwan. peyjiumc@mail.cgu.edu.tw
authors.forename: Pey-Jium
authors.initials: PJ
authors.lastname: Chang
authors.forename: Lee-Wen
authors.initials: LW
authors.lastname: Chen
authors.forename: Yan-Chung
authors.initials: YC
authors.lastname: Shih
authors.forename: Ping-Hsin
authors.initials: PH
authors.lastname: Tsai
authors.forename: An-Chi
authors.initials: AC
authors.lastname: Liu
authors.forename: Chien-Hui
authors.initials: CH
authors.lastname: Hung
authors.forename: Jieh-Yuan
authors.initials: JY
authors.lastname: Liou
authors.forename: Shie-Shan
authors.initials: SS
authors.lastname: Wang
mesh_terms: D002460:Cell Line; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D017735:Virus Latency; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D017874:Immediate-Early Proteins; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D050986:YY1 Transcription Factor; C494698:YY1 protein, human